Identification of Potential N-Myristoyltransferase Inhibitors from (L.) Dunal: A Molecular Docking and Molecular Dynamics Investigation.

Leishmaniasis is a group of infectious diseases caused by protozoa. The ineffectiveness, high toxicity, and/or parasite resistance of the currently available antileishmanial drugs has created an urgent need for safe and effective leishmaniasis treatment. Currently, the molecular-docking technique is used to predict the proper conformations of small-molecule ligands and the strength of the contact between a protein and a ligand, and the majority of research for the development of new drugs is centered on this type of prediction. N-myristoyltransferase (NMT) has been shown to be a reliable therapeutic target for investigating new anti-leishmanial molecules through this kind of virtual screening. Natural products provide an incredible source of affordable chemical scaffolds that serve in the development of effective drugs. leaves, roots, and fruits have been shown to contain withanolide and other phytomolecules that are efficient anti-protozoal agents against , and spp. Through a review of previously reported compounds from -afforded 35 alkaloid, phenolic, and steroid compounds and 132 withanolides/derivatives, typical of the genus. These compounds were subjected to molecular docking screening and molecular dynamics against NMT. Calycopteretin-3-rutinoside and withanoside IX showed the highest affinity and binding stability to NMT, implying that these compounds could be used as antileishmanial drugs and/or as a scaffold for the design of related parasite NMT inhibitors with markedly enhanced binding affinity.